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The Concentration of Glutathione in Human Erythrocytes is a Heritable Trait

van 't Erve, T.J., Wagner, B.A., Ryckman, K.K. et al.

Glutathione (GSH) is a ubiquitous, redox active, small molecule that is critical to cellular and organism health. In red blood cells (RBCs), the influence of the environment (e.g. diet and lifestyle) on GSH levels has been demonstrated in numerous studies. However, it remains unknown if levels of GSH are determined principally by environmental factors, or if there is a genetic component, i.e. heritability. To investigate this we conducted a twin study. Twin studies are performed by comparing the similarity in phenotypes between mono- and di-zygotic twin pairs. We determined the heritability of GSH, as well as its oxidation product glutathione disulfide (GSSG), the sum of GSH equivalents (tGSH), and the status of the GSSG/2GSH couple (marker of oxidation status, Ehc) in RBCs. In our study population we found that the estimated heritability for the intracellular concentration of GSH in RBCs is 57 %; GSSG is 51 %, tGSH is 63 %, and Ehc is 70 %. We conclude that a major portion of the phenotype of these traits is controlled genetically. We anticipate that these heritabilities will also be reflected in other cell types. The discovery that genetics play a major role in the innate levels of redox active species in RBCs is paradigm-shifting and opens new avenues of research in the field of redox biology. Inherited RBC anti-oxidant levels may be important disease modifiers. By identifying the relative contributions of genes and the environment to anti-oxidant variation between individuals, new therapeutic strategies can be developed. Understanding the genetic determinants of these inherited traits may allow personalized approaches to relevant therapies.

Citation

van 't Erve, T.J., Wagner, B.A., Ryckman, K.K. et al. "The Concentration of Glutathione in Human Erythrocytes is a Heritable Trait" Free Radical Biology and Medicine (2013): 742–9